Coordinated regulation of calcium homeostasis and pathogenicity by a dual-action transcriptional regulator Cas5 [ChIP-Seq]

ABSTRACT: As a clinically relevant opportunistic human fungal pathogen, C. albicans is able to rapidly sense and adapt to changing microenvironments within the host, a process that is essential for its successful invasion and survival. Although studies have shown that the transcription factor Crz1 is the master regulator of calcium (Ca2+) homeostasis, accumulating evidence supports a clear involvement of other participants in this biological process. Here, following a high-throughput genetic screen, we identified the transcription factor Cas5 as a novel positive regulator of Ca2+ homeostasis in C. albicans. Mechanistically, Cas5 modulates Crz1 dephosphorylation, nuclear localization and Crz1-dependent signaling pathway by inhibiting protein kinase Tpk1 to maintain Ca2+ homeostasis. Furthermore, our study confirms that the calcineurin-mediated virulence is dependent on transcription factor Cas5 in a Crz1-independent manner, complementing a long-standing knowledge gap in the regulation of virulence by calcineurin. Taken together, our findings elucidate that a dual-action transcriptional regulator Cas5 coordinates both Ca2+ homeostasis and pathogenicity of C. albicans in the host.

ORGANISM(S): Candida albicans

PROVIDER: GSE295026 | GEO | 2026/04/18

REPOSITORIES: GEO